The human herpesviruses are grouped into three subfamilies: 1) the Alphaherpesvirinae, which includes human simplex virus 1 (HSV-1), human simplex virus 2 (HSV-2), and varicella-zoster virus; 2) the Betaherpesvirinae, which includes human cytomegalovirus (HCMV) human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7); and 3) the Gammaherpesvirinae, which includes Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) (Roizman, B. 1996. Herpesviridae, p. 2221-2230. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), Virology. Lippincott-Raven, Philadelphia, Pa.). Although the human herpesviruses generally cause asymptomatic infections in immuno-competent individuals, these viruses can cause severe, life-threatening infections in immuno-compromised individuals. In general, these viruses can be reactivated following primary exposure.
Members of the herpesvirus family have been implicated in the etiology of several human cancers. For example, EBV, HSV-2, HHV-6, HHV-8, and HCMV have been associated with cancers in a wide range of organ systems (Reviewed in Doniger et al., 1999. Clin. Microbiol. Rev. 12:367). However, the exact role of the herpesvirus family in cancer etiology is unknown and the data have failed to establish a causative link between specific disease states and individual viruses.
HCMV is endemic to the human population and persistently infects 70-95% of the US adult population. In healthy, immuno-competent adults, most HCMV infections are asymptomatic. In addition, about 0.5 to 2.5% of all newborns are infected at birth, with a majority of these infections being asymptomatic. However, in immuno-compromised individuals, HCMV can cause severe disseminated disease characterized by chorioretinitis, pneumonia, esophagitis, colitis, myelitis, meningitis, encephalitis, leukopenia, lymphocytosis, and hepatitis. HCMV infections can be reactivated following latentcy following blood transfusions, pregnancy, solid-organ or bone marrow transplantation, immunosuppressive therapy, or other viral infections. HCMV infects a wide range of cell types, including leukocytes, endothelial cells, connective tissue cells, and epithelial cells (Hirsch, M. S. 1984. Ser. 20:161; Myerson et al.1984. Hum. Pathol. 15:431; Rapp, F. 1984. JNCI 72:783). HCMV is transmitted through milk, semen, urine, saliva, and cervical secretions and may be acquired via the transplacental, perinatal, and sexual routes, through blood transfusion and organ or bone marrow transplantation.
A definitive role of HCMV in human cancer has not been established. The ubiquitous distribution of HCMV in the human population and the high seroconversion rates of HCMV make establishing a clear etiological association difficult. Furthermore, the large size of HCMV (230 kbp) makes the detection of small viral DNA sequences (1,000 bp) associated with the initiation or progression of cancer very difficult when a whole genomic probe is used.